Our recent studies in children confirm observations on lead workers that the red cell of both man and the rat contains a phosphorylase specific for pyrimidines, pyrimidine 5'-nucleotidase (EC 3.1.3.5; P5N). P5N dephosphorylates pyrimidine nucleotides, preventing accumulation in the red blood cell. It is inhibited by lead with a negative correlation that is significant even at low levels of blood lead (10-40 micron g %). We propose to examine the epidemiologic significance of P5N in preschool children identified and followed in the Omaha Childhood Lead Poison Program. In addition to assays of red cell P5N, the children will be surveyed for the presence of red cell cytidine and uridine phosphates, nucleotides which accumulate in deficiences of P5N. The accumulation of cytidine phosphate as metabolic debris may cause feedback inhibition of ribosomal degradation resulting in alteration of mRNA and, consequently, globin synthesis. This will be investigated by the correlation of P5N activity and of the intraerythrocytic accumulation of pyrimidines with measures of gamma and beta chain globin synthesis.